The biosynthesis of the Drosophila melanogaster eggshell is an excellent model system of coordinate gene expression in higher organisms. Our studies indicate that the program by which the eggshell proteins are made involves the time-specific, sequential uncoding of at least three sets of structural genes. Our long-term goal is to elucidate the chromosomal organization of coordinated sets of genes, including genetic elements involved in the control of their expression. The first steps, to define the system biochemically and to establish methodologies for experimental manipulations, have been completed. The second step is to locate the genes coding for the eggshell proteins. I propose to accomplish this task by utilizing the genetic wealth of Drosophila in two ways. First, I propose to identify natural variations in the eggshell proteins among the many different geographic strains of Drosophila using isoelectric focusing and SDS acrylamide gels; and then, to locate the structural genes for these variations using hybrid crosses and recombination analysis. Second, I propose to do a detailed biochemical, developmental and morphological characterization of the thirty or more existing female-sterile mutants which at a gross level are characterized as having defective eggshells in order to determine which of these have primary defects in eggshell proteins and whose genetic loci, therefore, should represent the structural genes for eggshell proteins. Identification of the locations of the eggshell genes may allow insights into the relationship between chromosomal arrangement and expression of genes, and will provide information needed for analysis of linked regulatory elements.